Macroscopic sweat test for cystic fibrosis

Abstract

The present invention relates to methods of diagnosing CF comprising: stimulating sweat production via β-adrenergic pathway, by increasing cAMP production; collecting sweat into a sweat collection device; determining the sweat rate as a function of the weight of the sweat collected; correlating the sweat rate with the functional state of CFTR and/or presence or absence of CF. The invention also relates to methods of screening compounds for treatment of cystic fibrosis.

What is claimed is: 
     
       1. A method of diagnosing cystic fibrosis in a patient comprising a) stimulating sweat production via β-adrenergic pathway;   b) collecting sweat into a sweat collection device for a predetermined amount of time;   c) determining the sweat rate as a function of the weight of the sweat collected;   d) correlating the sweat rate with the functional state of cystic fibrosis transmembrane conductance regulator and/or the presence or absence of cystic fibrosis.   
     
     
       2. The method according to claim 1, wherein the step of stimulating sweat production comprises injecting into the patient a solution comprising at least one β agonist. 
     
     
       3. The method according to claim 2, wherein the β agonist is selected from isoproterenol, albuterol, terbutaline and metaproterenol. 
     
     
       4. The method according to claim 2, wherein the solution further comprises a cAMP augmenting agent and an anticholinergic compound. 
     
     
       5. The method according to claim 4, wherein the cAMP augmenting agent is selected theophylline, aminophylline, and milrinone and the anticholinergic compound is selected from atropine, scopolamine, glycopyrrolate or ipratropium bromide. 
     
     
       6. The method according to claim 5, wherein the cAMP augmenting agent is theophylline or aminophylline and the anticholinergic compound is atropine. 
     
     
       7. The method according to claim 4, wherein the solution comprises isoproterenol, theophylline, and atropine. 
     
     
       8. The method according to claim 1, wherein the step of collecting sweat into a sweat collection device comprises absorbing sweat onto a sweat absorbing material. 
     
     
       9. The method according to claim 8, wherein the step of collecting sweat further comprises placing the sweat absorbing material into an air-tight transport container. 
     
     
       10. The method according to claim 1, wherein the step of determining the sweat rate comprises weighing the sweat collection device and dividing the amount of sweat by the time of collection. 
     
     
       11. The method according to claim 1, further comprising stimulating sweat production through the cholinergic pathway; collecting sweat into a sweat collection device; and determining the sweat rate as a function of the weight of the sweat collected. 
     
     
       12. A method of screening compounds for treatment of cystic fibrosis, comprising: a) providing a compound of interest to a test subject;   b) providing a composition to stimulate sweat production by the β-adrenergic pathway;   c) collecting sweat onto a sweat absorbing material; and   d) determining the sweat rate as a function of the weight of the sweat collected;   e) correlating the sweat rate with the functional state of cystic fibrosis transmembrane conductance regulator and/or presence or absence of cystic fibrosis.   
     
     
       13. A kit for measuring the sweat rate in a patient suspected of having cystic fibrosis, comprising: a) a composition to stimulate sweat production via the β-adrenergic pathway;   b) sweat absorbing material;   c) air-tight transport container; and   d) air-tight barrier.   
     
     
       14. The kit according to claim 13, wherein the composition to stimulate sweat productions comprises a β-agonist, a cAMP augmenting agent and an anti-cholinergic compound. 
     
     
       15. The kit according to claim 14, wherein the composition comprises isoproterenol, aminophylline and atropine. 
     
     
       16. The kit according to claim 13, further comprising methacholine. 
     
     
       17. The method according to claim 4, wherein the cAMP augmenting agent is methyl xanthine.